[Paper-level Aggregated] PMCID: PMC5792548

Evidence Type(s): Oncogenic

Summary: Mutation: T790M | Summary: The EGFR T790M mutation contributes to tumor development and progression, as it is implicated in acquired resistance to EGFR tyrosine kinase inhibitors and is maintained in osimertinib-resistant cells. It is also associated with gefitinib resistance in lung adenocarcinoma.

Evidence Type: Oncogenic Mutation: 19del | Summary: The EGFR exon 19 deletion (19del) is associated with tumor development and progression in lung cancer, as indicated by its presence in both naive and acquired gefitinib-resistant cell lines. It is also linked to gefitinib resistance in lung adenocarcinoma.

Evidence Type: Oncogenic Mutation: C797S | Summary: The C797S mutation contributes to tumor progression by conferring resistance to EGFR-TKIs, which is a characteristic of oncogenic behavior.

Gene→Variant (gene-first): EGFR(1956):T790M EGFR(1956):19del EGFR(1956):C797S

Genes: EGFR(1956)

Variants: T790M 19del C797S

[Paper-level Aggregated] PMCID: PMC5792548

Evidence Type(s): Predictive

Summary: Mutation: T790M | Summary: The EGFR T790M mutation is associated with resistance to the standard treatment osimeritinib in non-small cell lung cancer, indicating its predictive role in therapy response.

Evidence Type: Predictive Mutation: C797S | Summary: The C797S mutation is associated with resistance to osimertinib, indicating its role in therapy response.

Gene→Variant (gene-first): EGFR(1956):T790M EGFR(1956):C797S

Genes: EGFR(1956)

Variants: T790M C797S

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 14

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: T790M | Summary: The EGFR T790M mutation is maintained in osimertinib-resistant RPC-9/OsiR cells, indicating its role in tumor development or progression.

Gene→Variant (gene-first): 1956:C797S 1956:T790M

Genes: 1956

Variants: C797S T790M

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 10

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: 19del | Summary: The EGFR exon 19 deletion (19del) is associated with gefitinib resistance in lung adenocarcinoma, indicating its role in tumor development and progression. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation in EGFR is implicated in gefitinib resistance in lung adenocarcinoma, contributing to tumor development and progression.

Gene→Variant (gene-first): 1956:19del 1956:T790M

Genes: 1956

Variants: 19del T790M

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: 19del | Summary: The EGFR exon 19del mutation is associated with the development of resistance in lung cancer cells, indicating its role in tumor progression.

Gene→Variant (gene-first): 1956:19del

Genes: 1956

Variants: 19del

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 4

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: C797S | Summary: The C797S mutation is associated with resistance to osimertinib, indicating its role in therapy response. Evidence Type: Oncogenic | Mutation: C797S | Summary: The C797S mutation contributes to tumor progression by conferring resistance to EGFR-TKIs, which is a characteristic of oncogenic behavior.

Gene→Variant (gene-first): 1956:C797S

Genes: 1956

Variants: C797S

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 3

Evidence Type(s): Oncogenic

Summary: Evidence Type: Oncogenic | Mutation: 19del | Summary: The EGFR exon 19 deletion (19del) is associated with tumor development and progression in lung cancer, as indicated by its presence in both naive and acquired gefitinib-resistant cell lines. Evidence Type: Oncogenic | Mutation: T790M | Summary: The T790M mutation is implicated in tumor development and progression, as it is found in acquired gefitinib-resistant lung cancer cells, indicating its role in resistance mechanisms.

Gene→Variant (gene-first): 1956:19del 1956:T790M

Genes: 1956

Variants: 19del T790M

[Paragraph-level] PMCID: PMC5792548 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Oncogenic

Summary: Evidence Type: Predictive | Mutation: T790M | Summary: The EGFR T790M mutation is associated with resistance to the standard treatment osimeritinib in non-small cell lung cancer, indicating its predictive role in therapy response. Evidence Type: Oncogenic | Mutation: T790M | Summary: The EGFR T790M mutation contributes to tumor development and progression, as it is implicated in acquired resistance to EGFR tyrosine kinase inhibitors.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paper-level Aggregated] PMCID: PMC5792548

Evidence Type(s): Oncogenic, Predictive, Functional

Justification: Oncogenic: The presence of the EGFR T790M mutation is associated with resistance to EGFR TKIs, indicating its role in tumorigenesis and treatment resistance in non-small cell lung cancer. Predictive: The EGFR T790M mutation is used to predict the efficacy of third-generation EGFR TKIs like osimertinib, as it is a known biomarker for response to this treatment. Functional: The study investigates the functional consequences of various mutations, including T790M and C797S, on the resistance mechanisms of lung cancer cells to EGFR TKIs, demonstrating their impact on cell proliferation and signaling pathways.

Gene→Variant (gene-first): EGFR(1956):19del EGFR(1956):T790M EGFR(1956):C797S

Genes: EGFR(1956)

Variants: 19del T790M C797S

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 14

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the effects of combination therapies on cell proliferation in osimertinib-resistant cell lines, indicating a relationship between the presence of the T790M mutation and the response to therapy, specifically mentioning osimertinib and naquotinib. Oncogenic: The T790M mutation is maintained in the osimertinib-resistant RPC-9/OsiR cells, suggesting its role in tumor development or progression, particularly in the context of resistance to therapy.

Gene→Variant (gene-first): 1956:C797S 1956:T790M

Genes: 1956

Variants: C797S T790M

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses gefitinib-resistant lung adenocarcinoma cell lines harboring the EGFR exon 19del and T790M mutations, indicating a correlation with resistance to therapy, specifically gefitinib. Oncogenic: The mention of the EGFR exon 19del and T790M mutations in the context of gefitinib resistance suggests that these somatic variants contribute to tumor development or progression in lung adenocarcinoma.

Gene→Variant (gene-first): 1956:19del 1956:T790M

Genes: 1956

Variants: 19del T790M

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic, Predictive

Justification: Oncogenic: The passage discusses the role of the EGFR exon 19del variant in the development of a resistant cell line, indicating that this somatic variant contributes to tumor progression and resistance mechanisms in lung cancer cells. Predictive: The passage mentions that the combination of EGFR-TKIs and MET inhibitors showed an excellent inhibitory effect on cell proliferation in the resistant cell line, suggesting a correlation between the variant and response to therapy.

Gene→Variant (gene-first): 1956:19del

Genes: 1956

Variants: 19del

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 4

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the acquired EGFR C797S mutation in the context of resistance to osimertinib, indicating that this variant correlates with resistance to a specific therapy. Oncogenic: The C797S mutation is described as contributing to resistance in cell lines, suggesting its role in tumor progression or development in the context of EGFR-TKI treatment.

Gene→Variant (gene-first): 1956:C797S

Genes: 1956

Variants: C797S

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the establishment of naquotinib-resistant lung cancer cells and mentions the effectiveness of naquotinib in inhibiting cell proliferation, indicating a correlation between the variants (19del and T790M) and resistance to therapy. Oncogenic: The presence of the T790M mutation in acquired gefitinib-resistant cells suggests that it contributes to tumor development or progression, as it is associated with resistance mechanisms in lung cancer.

Gene→Variant (gene-first): 1956:19del 1956:T790M

Genes: 1956

Variants: 19del T790M

[Paragraph-level] PMCID: PMC5792548 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses the EGFR T790M mutation in the context of treatment response to osimeritinib and the development of resistance, indicating a correlation with therapy outcomes. Diagnostic: The passage states that the EGFR T790M mutation is used to identify patients with non-small cell lung cancer who are eligible for treatment with osimeritinib, thus classifying it as a diagnostic marker. Oncogenic: The EGFR T790M mutation is described as contributing to resistance in lung cancer, which implies its role in tumor progression and development.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 14

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the effects of combination therapies on cell proliferation in osimertinib-resistant cell lines, indicating a relationship between the presence of the T790M mutation and the response to therapy, specifically mentioning osimertinib and naquotinib. Oncogenic: The T790M mutation is maintained in the osimertinib-resistant RPC-9/OsiR cells, suggesting its role in tumor development or progression, particularly in the context of resistance to therapy.

Gene→Variant (gene-first): 1956:C797S 1956:T790M

Genes: 1956

Variants: C797S T790M

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 10

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses gefitinib-resistant lung adenocarcinoma cell lines harboring the EGFR exon 19del and T790M mutations, indicating a correlation with resistance to therapy, specifically gefitinib. Oncogenic: The mention of the EGFR exon 19del and T790M mutations in the context of gefitinib resistance suggests that these somatic variants contribute to tumor development or progression in lung adenocarcinoma.

Gene→Variant (gene-first): 1956:19del 1956:T790M

Genes: 1956

Variants: 19del T790M

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 8

Evidence Type(s): Oncogenic, Predictive

Justification: Oncogenic: The passage discusses the role of the EGFR exon 19del variant in the development of a resistant cell line, indicating that this somatic variant contributes to tumor progression and resistance mechanisms in lung cancer cells. Predictive: The passage mentions that the combination of EGFR-TKIs and MET inhibitors showed an excellent inhibitory effect on cell proliferation in the resistant cell line, suggesting a correlation between the variant and response to therapy.

Gene→Variant (gene-first): 1956:19del

Genes: 1956

Variants: 19del

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 4

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the acquired EGFR C797S mutation in the context of resistance to osimertinib, indicating that this variant correlates with resistance to a specific therapy. Oncogenic: The C797S mutation is described as contributing to resistance in cell lines, suggesting its role in tumor progression or development in the context of EGFR-TKI treatment.

Gene→Variant (gene-first): 1956:C797S

Genes: 1956

Variants: C797S

[Paragraph-level] PMCID: PMC5792548 Section: RESULTS PassageIndex: 3

Evidence Type(s): Predictive, Oncogenic

Justification: Predictive: The passage discusses the establishment of naquotinib-resistant lung cancer cells and mentions the effectiveness of naquotinib in inhibiting cell proliferation, indicating a correlation between the variants (19del and T790M) and resistance to therapy. Oncogenic: The presence of the T790M mutation in acquired gefitinib-resistant cells suggests that it contributes to tumor development or progression, as it is associated with resistance mechanisms in lung cancer.

Gene→Variant (gene-first): 1956:19del 1956:T790M

Genes: 1956

Variants: 19del T790M

[Paragraph-level] PMCID: PMC5792548 Section: ABSTRACT PassageIndex: 1

Evidence Type(s): Predictive, Diagnostic, Oncogenic

Justification: Predictive: The passage discusses the EGFR T790M mutation in the context of treatment response to osimeritinib and the development of resistance, indicating a correlation with therapy outcomes. Diagnostic: The passage states that the EGFR T790M mutation is used to identify patients with non-small cell lung cancer who are eligible for treatment with osimeritinib, thus classifying it as a diagnostic marker. Oncogenic: The EGFR T790M mutation is described as contributing to resistance in lung cancer, which implies its role in tumor progression and development.

Gene→Variant (gene-first): 1956:T790M

Genes: 1956

Variants: T790M